Ignite Creation Date:
2024-05-06 @ 12:44 AM
Last Modification Date:
2024-10-26 @ 10:54 AM
Study NCT ID:
NCT01647945
Status:
COMPLETED
Last Update Posted:
2016-10-05
First Post:
2012-07-18
Brief Title:
FK506 Tacrolimus in Pulmonary Arterial Hypertension
Sponsor:
Edda Spiekerkoetter
Organization:
Stanford University
Study Overview
Official Title:
Single-Center Randomized Controlled Phase II Study of Safety and Efficacy of FK-506 Tacrolimus in Pulmonary Arterial Hypertension
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TransformPAH
Brief Summary:
Mutations in bone morphogenetic protein receptor 2 BMPR2 are present in 80 of familial and 20 of sporadic pulmonary arterial hypertension PAH patients Furthermore dysfunctional BMP signaling is a general feature of pulmonary hypertension even in non-familial PAH
We therefore hypothesized that increasing BMP signaling might prevent and reverse the disease We screened 3500 FDA approved drugs for their propensity to increase BMP signaling and found FK506 Tacrolimus to be a strong activator of BMP signaling Tacrolimus restored normal function of pulmonary artery endothelial cells prevented and reversed experimental PAH in mice and rats
Given that Tacrolimus is already FDA approved with a known side-effect profile it is an ideal candidate drug to use in patients with pulmonary arterial hypertension
The aims of our trial are
1 Establish the Safety of FK506 in patients with PAH
2 Evaluate the Efficacy of FK506 in PAH
3 Identify ideal candidates for future FK506 phase III clinical trial
We therefore hypothesized that increasing BMP signaling might prevent and reverse the disease We screened 3500 FDA approved drugs for their propensity to increase BMP signaling and found FK506 Tacrolimus to be a strong activator of BMP signaling Tacrolimus restored normal function of pulmonary artery endothelial cells prevented and reversed experimental PAH in mice and rats
Given that Tacrolimus is already FDA approved with a known side-effect profile it is an ideal candidate drug to use in patients with pulmonary arterial hypertension
The aims of our trial are
1 Establish the Safety of FK506 in patients with PAH
2 Evaluate the Efficacy of FK506 in PAH
3 Identify ideal candidates for future FK506 phase III clinical trial
Detailed Description:
Study Design
Randomized placebo-controlled four arm clinical trial
Sample Size 10 subjects in each arm Total enrollment 40 patients
1 10 patients FK-506 blood level 3 - 5 ngml
2 10 patients FK-506 blood level 2 - 3 ngml
3 10 patients FK-506 level 20 ngml
4 10 patients Placebo
Study Duration
16 weeks
Primary Endpoints
1 Safety of low-dose FK506 in PAH
Secondary ObjectivesEndpoints
1 Combined Clinical EventsTime to Clinical Worsening 16 weeks
All cause mortality
Transplantation
Atrial septostomy
Need for escalation of therapies as deemed by site investigator
Worsening of NYHAWHO classification by at least 1 point
Hospitalization for right heart failure
2 Change in 6MWD at 16 weeks
3 Change in NT-Pro-BNP at 16 weeks
4 Change in Uric Acid at 16 weeks
5 Change in DLCO at 16 weeks
6 Change in novel RV parameters by transthoracic echocardiography Change in RV size RA size RV function TAPSE RVSP
Randomized placebo-controlled four arm clinical trial
Sample Size 10 subjects in each arm Total enrollment 40 patients
1 10 patients FK-506 blood level 3 - 5 ngml
2 10 patients FK-506 blood level 2 - 3 ngml
3 10 patients FK-506 level 20 ngml
4 10 patients Placebo
Study Duration
16 weeks
Primary Endpoints
1 Safety of low-dose FK506 in PAH
Secondary ObjectivesEndpoints
1 Combined Clinical EventsTime to Clinical Worsening 16 weeks
All cause mortality
Transplantation
Atrial septostomy
Need for escalation of therapies as deemed by site investigator
Worsening of NYHAWHO classification by at least 1 point
Hospitalization for right heart failure
2 Change in 6MWD at 16 weeks
3 Change in NT-Pro-BNP at 16 weeks
4 Change in Uric Acid at 16 weeks
5 Change in DLCO at 16 weeks
6 Change in novel RV parameters by transthoracic echocardiography Change in RV size RA size RV function TAPSE RVSP
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None